The compounds of formula (I) are useful starting materials for the preparation of β-santalol ((Z)-2-methyl-5-((1SR,2RS,4RS)-2-methyl-3-methylenebicyclo[2.2.1]heptan-2-yl)pent-2-en-1-ol, i.e. the exo isomer), and derivatives thereof, in a very short, effective and industrially feasible manner.
The β-santalol, and derivatives thereof, are well known and highly valued perfuming ingredients, some of which have particular relevance. Synthetic β-santalol is not commercially available at this time and it is only available from natural sources (Sandalwood sp. essential oils). β-santalol is present in East Indian Sandalwood Oil (Santalum album) at a typical level of 20-25% and is generally accepted as the principal odor vector for the fine creamy sandalwood character of the essential oil. The West Australian Sandalwood Oil (Santalum spicatum.) typically contains much less β-santalol, in the range of 3-8% of the essential oil, and as a result is a less appreciated oil.
The export of East Indian sandalwood and the distillation of the essential oil is under strict government control since Santalum Album has been classified by the Convention on International Trade in Endangered Species of Wild Fauna and Flora and International Union for Conservation of Nature Red list as vunerable and at risk of extinction.
Therefore, there is an urgent need for alternative syntheses to produce β-santalol and its derivatives.
To the best of our knowledge, all known syntheses are lengthy or require expensive starting materials and/or reagents or even steps which are too expensive for an industrial process or generate unacceptable quantities of waste (e.g. see Brunke at al., in Rivista Italiana EPPOS, 1997, 49). In particular one may cite the following references, which are representative of the best examples of processes for the preparation of β-santalol:                EP 10213: however said process, besides the fact that it is very long, requires many chlorinated intermediates (not optimal for a use in perfumery) and provides a very low overall yield for the preparation of an enal which still requires several steps to be converted into the desired product;        A. Krotz et al, in Tet.Asymm., 1990, 1, 537: a relatively short synthesis, however it requires expensive reducing reagents that are difficult to manipulate on large scale, expensive chiral auxillaries and two Wittig reactions, and then subsequent transformation of a ketone into the exo-methylene group;        U.S. Pat. No. 3,662,008 and U.S. Pat. No. 3,679,756 (P&G) also describe the synthesis of β-santalol in low overall yield. This route is also dependent on a Wittig reaction to install the Z double bond and expensive reducing agents;        WO2009/141781: reports a synthesis of some derivatives of formula (I), used as intermediates in the preparation of santalol; however said synthesis is long and still passes through the same key enal intermediate as described in EP 10213.Thus, there is a need for improved processes for the preparation of β-santalol and these are now provided by the present invention.        